Amphetamine Use Disorders

Michael Mancino, M.D.

University of Arkansas for Medical Sciences

(Title Slide)

I.        Introduction: (Slide 2)

A.      Lifetime use of substances is very common 

1.   Alcohol = 80 %

2.   Cannabinoids = 40 %

3.   Cocaine =  15 %

4.   Amphetamines (amphet) = 10 %

B.      Lifetime problems in users: minor (e.g. - missing work) [1]

1.   Alcohol ≈ 60 %

2.   Cannabinoids and cocaine ≈ 50 %

3.   Amphet ≈ 60 %

C.      Problems arise because drugs (Slide 3)

1.   Mimic medical and psychiatric diagnoses

2.   ↑ symptoms in those with pre-existing diagnoses

3.   Cause direct side effects

4.   Rates ↑ in patient populations

a.      Are group with problems

b.      Seeking help

c.       E.g., for alcohol ≈ 80 %

5.   Doctors inadequately trained to recognize problems [2]

D.     Amphet are particularly concerning

1.   Recent ↑ in use  0.6 % in 2002 to 1.7 % in 2009 [3]

2.   Among the most likely to cause problems  

E.      This talk will review (Transition Slide 4)

1.   History and nature of amphet

2.   Epidemiology

3.   Problems

4.   Treatment

II.          History/nature of amphet

A.      History (Slide 5)

1.   First synthesized in 1887 by Dr. Edeleua working on bronchodilator: [4]

2.   CNS actions not reported until much later (1933)

3.   More common form of today, methamphetamine synthesized 1919

4.   Amphet popular as Over The Counter (OTC) bronchodilator in early 1930’s

5.   Non-medical stimulant misuse → “prescription only” status 1937

6.   WWII amphet used to ↑ performance[5]

a.      Early in WWII Germans used most amphet (Blitzkrieg: 1939-40)

1)      Leaders use of amphetamines → philosophy of stealth prominent in air attacks

2)      ↑ missions flown

b.      Mid war British used most amphet (early 1942)

1)      ↓ use as war went on

2)      Controversy re performance enhancement with long-term use

3)      Felt to ↓ judgment

4)      ↑ unnecessary risk taking in battle

c.       Americans started late 1942

1)      Pilots and troops: ↑ mood and alertness

2)      U.S. not acknowledge problem

d.      Japanese troops used throughout war

1)      To rebuild, work long hours

2)      Military stockpile released by US → available without script

3)      Decade of misuse in Japan after the war (>2 % population misusing)

7.   FDA ban of inhalers 1959 after intravenous (IV) use

8.   Amphet moved to schedule II 1970 to ↓ misuse

a.      Schedule II: controlled regulation by federal US drug policy

1)      High potential for misuse → dependence

2)      Also legitimate medical use

b.      But not schedule I

1)      High potential for misuse → dependence

2)      No legitimate medical use (e.g., heroin)

B.      Drug classification based on usual effects (Slide 6) [6]

1.   Depressants → ↑ sleep, give a high like alcohol, associated with disinhibition

a.      Alcohol

b.      Benzodiazepines (e.g. diazepam [Valium])

2.   Cannabinoids → ↓ drive, ↑ appetite

3.   Opioids → ↓ pain, ↓ cough

a.      Heroin

b.      Most prescription pain pills

4.      Stimulants (to discuss below)

a.      Amphet (in all forms)

b.      Cocaine (in all forms)

c.       Medications for Attention Deficit Hyperactivity Disorder (ADHD) - disorder of focus

1)    Methylphenidate (Ritalin, Concerta, Methylin)

2)   Dextroamphetamine (Dexedrine, Dextrostat)

3)   Mixed amphetamine salts (Adderall)

4)   Lisdexamfetamine (Vyvanse)

d.      Most Rx weight reducing pills

C.      Amphet are typical stimulants

1.   Can be ingested by: (Slide 7) [7]

a.      Oral pills (slower onset and milder high)

b.      Nasally – snorting (faster onset/more intense high)

c.       Intravenous – IV (fastest/most intense high, most overdose)

1)      Faster/more intense the high → more likely to use again

2)      More difficult to stop using

d.      Amphet high is short-lived

1)      High lasts < 1 hour

2)      Drug half-life = 12-13 hours

3)      Post high letdown → feel more sad than before

a)       Withdrawal effect

b)      Opposite of acute effect

c)      Will discuss in more detail later

4)      Can alleviate sadness by using more drug

2.   Also known as psychostimulants → act on mental processes → affect behavior (Slide 8)

a.      Temporary ↑ in energy and focus attention

b.      Temporary ↑ in physical activity level

1)      Endurance

2)      Locomotion – walk faster

3.   Structure: like adrenaline = epinephrine (Slide 9)

4.   Hormone responsible for “fight or flight” (Slide 10)

a.      Bind to adrenoreceptors (sympathetic nervous system) throughout body

b.      ↑ body’s defense system

a.      Releases glucose → energy for action

b.      Shunt blood from gut → brain, heart, lungs, muscles

c.       Improves efficiency of these organs in response to stress

1)      Alpha adrenergic receptor binding → vasoconstriction

2)      Beta adrenergic binding → bronchodilation

5.   Acute → prominent brain (Central Nervous System-CNS) stimulation

a.      Euphoria

b.      ↓ need for sleep

c.       ↓ appetite

d.      ↑ focus of attention

6.   CNS actions through → ↑ neurotransmitters (NTS) in nerve ending (Slide 11) [8]

a.      Block re-uptake pumps or transporters

1)      Similar to cocaine

2)      More NTS remains active in synapse

3)      NTS

                                                                              a)      Norepinephrine – physiological arousal

                                                                              b)      Dopamine – reward, psychosis

                                                                              c)      Serotonin – mood elevation, ↑ doses → psychosis

b.      Taken up in pre-synaptic nerve ending in exchange for NTS (Slides 12-16)

1)      Amphet

2)      Once inside nerve ending taken up by intracellular vesicles

3)      ↑ release of NTS in the nerve ending → ↑ NTS for release to synapse

D.     Lecture emphasizes problems, but some medical uses exist (Slide 17)

1.   Narcolepsy – sleep disorder → frequent daytime sleep attacks [3]

a.      Medications to ↑ wakefulness

b.      Mild CNS stimulants [9]

1)      Modafinil (Provigil): 200-400mg daily

2)      Armodafinil (Nuvigil): 150-250mg daily

3)      Sodium oxybate (Xyrem): 6-9 grams/night

2.   Attention Deficit Hyperactivity Disorder (ADHD)

a.      Children ↓ attention, ↑ activity/impulsivity

b.      Responds to relatively low med doses to ↑ attention & ↓over-activity [9]

1)      Amphet/dextroamphetamine (Adderall)

a)      Standard dose: 5-20 mg/day

b)      Euphoric dose: > 60 mg/day, less if drug naive

2)      Methylphenidate (Ritalin)

a)      Standard dose: 10-40 mg/day

b)      Euphoric dose: > 100mg/day, less if drug naive

E.      Non-prescribed use common and dangerous (Transition Slide 18)

1.   Have discussed the history and nature of amphet

2.   Will discuss high prevalence non-prescribed use

3.   Review associated problems

III.    Epidemiology of non-medical use (Slide 19) [3]

A.      Lifetime use in US in 2009 ≈ 9% overall

1.      Highest rate age 26-34 (>12%)

2.      Rate males = females (10 % / 8 %)

3.      Rate 2X > white than black

B.      Past month use ≈ 0.5 %

C.      Lifetime rate of dependence ≈ 1.5 %

1.      Drug dependence is > 3 in 12 months (Slide 20) [10]

a.      Tolerance: need ↑ amount for desired effect

b.      Withdrawal

c.       Use larger amts/longer than intended

d.      Desire or attempts to cut down

e.      Much time spent to obtain, use or recover

f.        Give up activities

g.      Ongoing use despite problems

2.      Drug abuse is > 1 in 12 months (Slide 21) [10]

a.      Inability to fulfill role obligations

b.      Use in physically hazardous situations

c.       Legal problems

d.      Social or interpersonal problems

e.      Never met criteria for dependence

D.     Additional epidemiologic data 2009 [3]

1.      US: 1.3 million non-medical users of amphet past month

2.      US: 150,000 new users of methamphetamine past year

3.      US: 500,000 treated past year

(Transition Slide 22)

IV.       Amphet problems (Slide 23)

A.      Medical

1.      Overdose (Slide 24)

a.      100-200 mg dextroamphetamine if non-tolerant

b.       > 1 gram in chronic users

c.       Physical signs and symptoms [11, 12]

1)      Sympathetic nervous system over-activity (Slide 25)

a)      ↑ heart rate (>100 beats per min)

b)      ↑blood pressure (> 160 systolic or > 110 diastolic)

c)      ↑ respiratory rate (> 30/min)

d)      ↑ body temperature (> 1020)

e)      Dilated pupils

f)       Seizures

g)      Chest pain → myocardial ischemia → heart attack → death (Slide 26)

h)      Stroke → can be fatal

i)        Arrhythmias → can be fatal

j)        Muscle rigidity, delirium, agitation → cardiovascular shock

2)      Psychological effects (Slide 27)

a)      Restlessness

b)      Dizziness

c)      Irritability → violence

d)      Insomnia

e)      Higher doses →

  Suspiciousness

  Stereotypy (body rocking, pacing, crossing/uncrossing legs)

  Bruxism (grinding of teeth)

  Punding (repetitive touching and picking at objects/body parts) → open sores

d.      Treatment (Slide 28) [11, 12]

1)      Basic Life support functions- Airway, Breathing and Circulation

2)      Oral overdose: limited role  gastric lavage (pump stomach)– most absorbed by time seen

3)      Control ↑ temp (hyperthermia)

a)      Ice packs

b)      Cooling blanket

c)      Dantroline (Dantrium): 1-2mg/kg/ 4 times daily

4)      Control seizures (diazepam): 10mg IV, repeat as needed every few minutes

5)      Control ↑ blood pressure: phentolamine (Regitine): 5-15mg IV

6)      Chest pains/heart attack: aspirin, nitrates, morphine or benzodiazepines

7)      Urine toxicology to ID other drugs

8)      Medication for agitation (Slide 29)

a)      Benzodiazepines (if NOT psychotic)

   Diazepam (Valium): 10-30mg PO, 2-10 mg by mouth or IV

   Lorazepam (Ativan): 2-4 mg PO, IM, IV

b)      High potency antipsychotics (avoid anticholinergic side effects)

   Haloperidol (Haldol): 5-10 mg PO, IM, IV

   Risperidone (Risperdal): 2-4 mg PO

2.      Withdrawal is typical of stimulants [13, 14] (Slide 30)

a.      Begins within > 2 hours after last use

b.      Peaks on day 1-2

c.       Symptoms opposite of intoxication

1)      Sleepy

2)      Depressed

3)      ↑ appetite

4)      ↓ concentration

5)      Craving

d.      Symptoms ↓ over 3-4 days

e.      Mild ↓ concentration + ↑ sadness can last for > 2 months

3.      Other medical problems (Slide 31)

a.      IV → Infection (use of contaminated needles)

1)      Endocarditis – inflammation of inside lining of heart chambers and valves

2)      Skin abscesses

3)      HIV → AIDS [15]

a)      ↑in men who have sex with men → ↑ risky sexual behaviors

   HIV general population 0.4%

   Men who have sex with men > 7.0 %

b)      Amphet → ↑ replication of HIV virus

b.      Intranasal → Holes in nasal septum

1)      Snorting → ↓ blood to lining/cartilage of septum

2)      Death of tissue in septum → hole develops

c.       Heart attack & stroke (can occur with acute and chronic use)

1)      Heart attack [16]

a)      ↑ heart rate → fatal arrhythmia (irregular heart beat)

b)      Cardiac blood vessel spasm → ↓ blood flow to heart

2)      Stroke [17]

a)      Ischemic stroke → intracranial blood vessel spasm similar to cardiac

b)      Intracranial bleeding → results from very high blood pressures

B.      Psychiatric (Slide 32)

1.      Stimulant induced psychosis

a.      Occurs in 25 % of users [18]

b.      Resembles acute schizophrenia

1)      Hallucinations (e.g., hear voices, skin crawling, see things)

2)      Delusions (e.g., people out to get them, special powers)

a)      Little insight → violence

b)      Japan post WW II epidemic → ½ convicted murders associated with misuse [12]

3)      Clear sensorium (alert and oriented)

4)      Different than schizophrenia (Slide 33)

a)      Schizophrenia – bland mood, develops slowly, rare abnormal physical findings

b)      Amphet induced – labile mood, develops rapidly, typical physical findings

5)      Stopping stimulants → psychosis resolved days to a week (rarely 1 month)

6)      Hallucination resolve 1st → delusions later

c.       Treatment [4, 11, 19] (Slide 34)

1)      Drug use history: drug toxicology to r/o other drugs; need screen for physical pathology

2)      Often need hospitalization

3)      Monitor vitals and treat as necessary

4)      ART: mnemonic for behavioral approach to help prevent escalation to violence

a)      Acceptance: immediate needs of patient

b)      Reassurance: condition due to drug and will resolve in a few hours

c)      Talkdown: reality orientation and avoid hostility

5)      May require physical restraints for patient/staff safety

6)      Antipsychotics in doses as outlined above (e.g.- haloperidol: 5-10 mg PO/IM/IV)

7)      Avoid benzodiazepines when psychotic (disinhibition)

8)      Refer for drug rehab

2.   Anxiety and depression

a.      Symptoms reported in 2/3 stimulant dependent persons [20]

b.      Anxiety (Slide 35)

1)      Intoxication (mimic panic attacks – attacks of fear with rapid onset)

a)      ↑ Heart rate

b)      Palpitations

c)      Nervousness

d)      Hyperventilation

2)      Obsessive-compulsive picture

a)      Take apart and reassemble mechanical objects

b)      High levels of use

c.       Depression (Slide 36)

1)      Often related to withdrawal

2)      “Atypical depression” where sleep/eat opposite of most depressions

a)      Impaired mood

b)      Sleepiness

c)      Excessive appetite

3)      Cessation → mood swings weeks to months

d.      Treatment (Slide 37)

                                                         1)      Counseling for drug use disorder discussed in more detail later

                                                         2)      Reassure patient

                                                         3)      Medication rarely necessary

                                                         4)      Evaluate for medical illness mimics panic

a)      Heart attack

b)      Hyperthyroidism (elevated thyroid hormone)

                                                         5)      Rule out pre-existing psychiatric disorders (e.g.- depression or anxiety disorders)

 (Transition Slide 38)

V.          Treatment/rehabilitation [12]

A.      Goals (Slide 39)

1.   Free of the drug forever, if possible

2.   Interim goals to ↓

a.      Use of amphet

b.      Risk HIV and other med issues

c.       Unemployment

d.      Crime

3.   To engage in treatment

B.      Rehab focused on: (Slide 40)

1.   Engaging dependent persons in treatment

2.   Supporting abstinence

3.   Prevent/reduce extent of relapse

4.   Build life management skills

5.   Learn to cope with anxiety and stress

C.      Rehab through: (Slide 41)

1.   Individual counseling

2.   Group (e.g., educational, relapse prevention)

3.   Urine toxicology (objective monitoring for relapse)

4.   Psychosocial treatments

a.      Contingency management (incentives for treatment and or abstinence)

b.      Motivational interviewing

1)      Client-centered, directive

2)      Enhance intrinsic motivation to change

3)      Explore and resolve ambivalence

c.       Cognitive behavioral therapy (CBT)

1)      “Talk therapy”

2)      Based on changing thinking and behaviors

3)      Thoughts responsible for feelings and behaviors

4)      Changing thoughts leads to more adaptive behaviors

5)      Teach, encourage and support

d.      Introduce patient to self-help groups → alcoholics or cocaine anonymous (AA or CA)

1)      Educational – find similarities to others problems with substances

2)      Free

3)      Emphasize abstinence – only requirement desire to quit substance

4)      Sober support

e.      Vocational rehabilitation

D.     Medications (Slide 42)

1.   Adjunct for other substance use disorders (e.g., alcohol, opiates)

2.   No clearly efficacious meds for stimulant use disorders

VI.       Summary of what we have covered (Slide 43)

1.   Amphet are stimulating drugs

2.   Amphet use disorders are common and cause serious problems

3.   Problems mimic medical and psychiatric conditions

4.   Treatment often required for acute effects as well as chronic use disorders

 


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